Childhood obesity prevalence has increased significantly over the past three decades. Obese children are 4-6 times more likely to become overweight or obese adults with greater risk of metabolic co-morbidities, such as non-alcoholic fatty liver disease (NAFLD). In U.S. children NAFLD prevalence is estimated to be 9%, but increases to 38% among obese children. Early stage hepatic steatosis is characterized by lipid accumulation, insulin resistance, and elevated levels of oxidative stress in the liver. Prenatal exposure to chemical and dietary factors can impact metabolic programming via epigenetic mechanisms, altering metabolic responses across life. A similar reprogramming mechanism may alter oxidative stress responses in offspring following in utero exposures, but this has not been studied. Using an in vivo mouse model, this proposal investigates mechanisms contributing to in utero exposures to endocrine disrupting chemicals, e.g. bisphenol A (BPA), and high fat Western and Mediterranean diets and altered oxidative stress and insulin response in adolescence and adulthood. While BPA and high fat diet (HFD) exposures in adulthood have been associated with increased oxidative stress, their potential to impact lifelong risk of NAFLD via fetal epigenetic reprogramming of redox sensitive genes is not understood. Interactions of diet and toxicant exposures are not commonly studied; thus the proposed model will provide novel insight into the ability of diets to mitigate or exacerbate intracellular and genomic alterations resulting from prenatal exposures. Measuring multiple types of tissue-specific oxidative responses (e.g. redox potentials, protein thiol oxidation, lipid oxidation) in mouse live and blood samples will provide insight into the effects that concurrent prenatal BPA and HFD exposures have on redox- regulated insulin resistance, gene methylation and expression, and subsequent changes in lipid composition, longitudinally across sensitive life stages. Fetal programming of oxidative stress and insulin response has wide-ranging implications for chronic diseases, including NAFLD. Improved understanding of this early life programming and the ability of diet to mitigate detrimental toxicant effects will promote development of prenatal intervention and prevention programs. This F31 Predoctoral Fellowship provides the opportunity to expand my current doctoral training and research potential. The primary goal is to build on my current multi-disciplinary research skills in epigenetics, toxicology, nutrition, and novel lipidomcs to study sensitive oxidative stress measurement techniques, data analysis methods of repeated measures, and merging large datasets. Career goals facilitated by this fellowship include protected time to learn methods for research translation to multiple audiences and to improve my leadership and management skills. The comprehensive training plan and proposed research project will examine a novel developmental pathway and mechanisms that could better explain the increase in oxidative stress response and its connection to insulin resistance across the population concurrent with rising incidence of chronic diseases, including obesity and NAFLD.